AU2019387494A1 - Methods for dosing and treatment of B cell malignancies in adoptive cell therapy - Google Patents
Methods for dosing and treatment of B cell malignancies in adoptive cell therapy Download PDFInfo
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CN110545826A (zh) | 2016-12-03 | 2019-12-06 | 朱诺治疗学股份有限公司 | 用于与激酶抑制剂组合使用治疗性t细胞的方法和组合物 |
KR20200054160A (ko) | 2017-06-02 | 2020-05-19 | 주노 쎄러퓨티크스 인코퍼레이티드 | 입양 세포 요법을 사용한 치료를 위한 물품 제조 및 방법 |
US12031975B2 (en) | 2017-11-01 | 2024-07-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
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CA3203531A1 (fr) | 2020-12-30 | 2022-07-07 | Simon Olivares | Vecteurs recombinants comprenant des cassettes d'expression polycistronique et leurs procedes d'utilisation |
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US4452773A (en) | 1982-04-05 | 1984-06-05 | Canadian Patents And Development Limited | Magnetic iron-dextran microspheres |
US5168062A (en) | 1985-01-30 | 1992-12-01 | University Of Iowa Research Foundation | Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence |
US4690915A (en) | 1985-08-08 | 1987-09-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adoptive immunotherapy as a treatment modality in humans |
US4795698A (en) | 1985-10-04 | 1989-01-03 | Immunicon Corporation | Magnetic-polymer particles |
IN165717B (fr) | 1986-08-07 | 1989-12-23 | Battelle Memorial Institute | |
US5219740A (en) | 1987-02-13 | 1993-06-15 | Fred Hutchinson Cancer Research Center | Retroviral gene transfer into diploid fibroblasts for gene therapy |
ATE114507T1 (de) | 1988-12-28 | 1994-12-15 | Stefan Miltenyi | Verfahren sowie materialien zur hochgraduierten magnetischen abspaltung biologischer materialien. |
US5200084A (en) | 1990-09-26 | 1993-04-06 | Immunicon Corporation | Apparatus and methods for magnetic separation |
FR2688138B1 (fr) | 1992-03-06 | 1995-05-05 | Rhone Poulenc Rorer Sa | Application de l'amino-2 trifluoromethoxy-6 benzothiazole pour obtenir un medicament destine au traitement de la sclerose laterale amyotrophique. |
EP0672144A1 (fr) | 1992-10-20 | 1995-09-20 | Chiron Corporation | Antagonistes du recepteur d'interleukine 6 |
US5827642A (en) | 1994-08-31 | 1998-10-27 | Fred Hutchinson Cancer Research Center | Rapid expansion method ("REM") for in vitro propagation of T lymphocytes |
WO1996013593A2 (fr) | 1994-10-26 | 1996-05-09 | Procept, Inc. | Recepteurs de lymphocites t monocatenaires solubles |
WO1996018105A1 (fr) | 1994-12-06 | 1996-06-13 | The President And Fellows Of Harvard College | Recepteur de lymphocyte t monocatenaire |
US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
DE19608753C1 (de) | 1996-03-06 | 1997-06-26 | Medigene Gmbh | Transduktionssystem und seine Verwendung |
US6451995B1 (en) | 1996-03-20 | 2002-09-17 | Sloan-Kettering Institute For Cancer Research | Single chain FV polynucleotide or peptide constructs of anti-ganglioside GD2 antibodies, cells expressing same and related methods |
US6123655A (en) | 1996-04-24 | 2000-09-26 | Fell; Claude | Cell separation system with variable size chamber for the processing of biological fluids |
WO1999018129A1 (fr) | 1997-10-02 | 1999-04-15 | Sunol Molecular Corporation | Proteines solubles du recepteur des lymphocytes t a chaine unique |
US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
WO1999060119A2 (fr) | 1998-05-19 | 1999-11-25 | Avidex, Ltd. | Complexes polyvalents de recepteurs de lymphocytes t |
WO2000014257A1 (fr) | 1998-09-04 | 2000-03-16 | Sloan-Kettering Institute For Cancer Research | Recepteurs de fusion specifiques a l'antigene prostatique specifique membranaire et ses utilisations |
WO2000023573A2 (fr) | 1998-10-20 | 2000-04-27 | City Of Hope | Cellules modifiees specifiques a la molecule cd20 et utilisation de ces dernieres pour l'immunotherapie cellulaires des malignites cd20?+¿ |
DE69919029T2 (de) | 1998-12-24 | 2005-09-08 | Biosafe S.A. | Vorrichtung zur bluttrennung, insbesondere zur konzentrierung von hematopoietischen stammzellen |
WO2001094944A2 (fr) | 2000-06-02 | 2001-12-13 | Memorial Sloan-Kettering Cancer Center | Cellules presentatrices d'antigene artificiel et leurs methodes d'utilisation |
DE60122765D1 (de) | 2000-11-07 | 2006-10-12 | Hope City | Cd19-spezifische umgezielte immunzellen |
US7070995B2 (en) | 2001-04-11 | 2006-07-04 | City Of Hope | CE7-specific redirected immune cells |
US20090257994A1 (en) | 2001-04-30 | 2009-10-15 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
ES2239246T3 (es) | 2001-08-31 | 2005-09-16 | Avidex Limited | Receptor soluble de celulas t. |
US7939059B2 (en) | 2001-12-10 | 2011-05-10 | California Institute Of Technology | Method for the generation of antigen-specific lymphocytes |
US20030170238A1 (en) | 2002-03-07 | 2003-09-11 | Gruenberg Micheal L. | Re-activated T-cells for adoptive immunotherapy |
US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
CA2497884C (fr) | 2002-09-06 | 2013-10-22 | Brian Varnum | Anticorps monoclonal therapeutique anti-il-1r1 humain |
JP4436319B2 (ja) | 2002-10-09 | 2010-03-24 | メディジーン リミテッド | 単鎖組換えt細胞レセプター |
US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
US20060058339A1 (en) | 2004-06-17 | 2006-03-16 | Ibrahim Prabha N | Compounds modulating c-kit activity and uses therefor |
DE602005022595D1 (de) | 2004-06-29 | 2010-09-09 | Immunocore Ltd | Einen modifizierten t-zellen-rezeptor exprimierende zellen |
US7645755B2 (en) | 2004-10-22 | 2010-01-12 | Janssen Pharmaceutical N.V. | Inhibitors of c-fms kinase |
ES2345837T3 (es) | 2005-03-23 | 2010-10-04 | Biosafe S.A. | Sistema integrado para la recogida, el procesamiento y el trasplante de subgrupos de celulas, incluyendo celulas madre adultas, para medicina regenerativa. |
KR101464424B1 (ko) | 2006-09-22 | 2014-11-27 | 파마시클릭스, 인코포레이티드 | 브루톤 티로신 키나제 억제제 |
WO2008063888A2 (fr) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Composés modulant l'activité de c-fms et/ou de c-kit et utilisations associées |
EP2680006A1 (fr) | 2007-02-08 | 2014-01-01 | Biogen Idec MA Inc. | Essais de criblage de NRF2 et procédés et compositions correspondants |
EP2537416B1 (fr) | 2007-03-30 | 2014-11-12 | Memorial Sloan-Kettering Cancer Center | Expression constitutive de ligands costimulants sur des lymphocytes T transférés de manière adoptive |
ES2660180T3 (es) | 2007-12-07 | 2018-03-21 | Miltenyi Biotec Gmbh | Sistemas y métodos para procesamiento de células |
US8479118B2 (en) | 2007-12-10 | 2013-07-02 | Microsoft Corporation | Switching search providers within a browser search box |
US9796987B2 (en) | 2007-12-11 | 2017-10-24 | The University Of North Carolina At Chapel Hill | Polypurine tract modified retroviral vectors |
US8507656B2 (en) | 2008-01-28 | 2013-08-13 | Medimmune Limited | Stabilized angiopoietin-2 antibodies and uses thereof |
WO2009099553A2 (fr) | 2008-02-01 | 2009-08-13 | The Regents Of The University Of California | Utilisation d’inhibiteur de kinase pour le traitement de l’athérosclérose |
US20120164718A1 (en) | 2008-05-06 | 2012-06-28 | Innovative Micro Technology | Removable/disposable apparatus for MEMS particle sorting device |
JP5173594B2 (ja) | 2008-05-27 | 2013-04-03 | キヤノン株式会社 | 管理装置、画像形成装置及びそれらの処理方法 |
HRP20211788T1 (hr) | 2008-08-26 | 2022-02-18 | City Of Hope | Postupak i pripravci za poboljšanje anti-tumorskog efektorskog funkcioniranja t stanica |
BRPI0918050A2 (pt) | 2008-09-19 | 2015-09-22 | Paratek Pharm Innc | compostos de tetraciclina para o tratamento de artrite reumatoide e metodos relacionados de tratamento |
TWI440469B (zh) | 2008-09-26 | 2014-06-11 | Chugai Pharmaceutical Co Ltd | Improved antibody molecules |
CA2676881C (fr) | 2008-09-30 | 2017-04-25 | Wyeth | Antagonistes de recepteurs opioides peripheriques, et leurs utilisations |
CA2777053A1 (fr) | 2009-10-06 | 2011-04-14 | The Board Of Trustees Of The University Of Illinois | Recepteurs de lymphocytes t a chaine unique humains |
EP4049674A1 (fr) | 2009-11-03 | 2022-08-31 | City of Hope | Récepteur du facteur de croissance épidermique tronqué (egfrt) pour la sélection de lymphocytes t transduits |
IL300955A (en) | 2010-06-03 | 2023-04-01 | Pharmacyclics Llc | (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-H1-pyrazolo[4,3-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1- Indicated for use as a drug to treat chronic lymphocytic leukemia or small lymphocytic lymphoma |
PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
NZ743310A (en) | 2011-03-23 | 2022-11-25 | Fred Hutchinson Cancer Center | Method and compositions for cellular immunotherapy |
EA023999B1 (ru) | 2011-05-05 | 2016-08-31 | Новартис Аг | Ингибиторы csf-1r для лечения опухолей головного мозга |
US8398282B2 (en) | 2011-05-12 | 2013-03-19 | Delphi Technologies, Inc. | Vehicle front lighting assembly and systems having a variable tint electrowetting element |
WO2013071154A1 (fr) | 2011-11-11 | 2013-05-16 | Fred Hutchinson Cancer Research Center | Immunothérapie par des lymphocytes t ciblant la cycline a1 pour le traitement du cancer |
ES2774160T3 (es) | 2012-02-13 | 2020-07-17 | Seattle Childrens Hospital D/B/A Seattle Childrens Res Institute | Receptores de antígenos quiméricos biespecíficos y usos terapéuticos de los mismos |
WO2013126726A1 (fr) | 2012-02-22 | 2013-08-29 | The Trustees Of The University Of Pennsylvania | Lymphocytes t doubles transgéniques comportant un car et un tcr, et leurs procédés d'utilisation |
US20150119267A1 (en) | 2012-04-16 | 2015-04-30 | Sloan-Kettering Institute For Cancer Research | Inhibition of colony stimulating factor-1 receptor signaling for the treatment of brain cancer |
CN104395462B (zh) | 2012-05-03 | 2017-09-26 | 弗雷德哈钦森癌症研究中心 | 增强亲和力的t细胞受体及其制备方法 |
CN104736178A (zh) | 2012-06-04 | 2015-06-24 | 药品循环公司 | 布鲁顿酪氨酸激酶抑制剂的晶形 |
GB201211310D0 (en) | 2012-06-26 | 2012-08-08 | Chroma Therapeutics Ltd | CSF-1R kinase inhibitors |
EP3824905B1 (fr) | 2012-08-20 | 2025-01-08 | Fred Hutchinson Cancer Center | Procédé et compositions pour l'immunothérapie cellulaire |
WO2014055668A1 (fr) | 2012-10-02 | 2014-04-10 | Memorial Sloan-Kettering Cancer Center | Compositions et procédés d'immunothérapie |
CN104781789B (zh) | 2012-12-20 | 2018-06-05 | 三菱电机株式会社 | 车载装置 |
CN105026553A (zh) | 2013-03-15 | 2015-11-04 | 干细胞技术公司 | 用于获得富集的间充质干细胞培养物的组合物和方法 |
TWI654206B (zh) | 2013-03-16 | 2019-03-21 | 諾華公司 | 使用人類化抗-cd19嵌合抗原受體治療癌症 |
CA2913052A1 (fr) | 2013-05-24 | 2014-11-27 | Board Of Regents, The University Of Texas System | Anticorps monoclonaux ciblant un recepteur d'antigene chimerique |
US9108442B2 (en) | 2013-08-20 | 2015-08-18 | Ricoh Company, Ltd. | Image forming apparatus |
RU2729463C2 (ru) | 2013-12-20 | 2020-08-06 | Фред Хатчинсон Кансэр Рисёч Сентер | Меченые химерные эффекторные молекулы и их рецепторы |
WO2015157399A1 (fr) * | 2014-04-10 | 2015-10-15 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Marqueurs génétiques de transgène et procédés d'utilisation |
CN113046312A (zh) | 2014-04-23 | 2021-06-29 | 朱诺治疗学股份有限公司 | 分离、培养和遗传工程改造用于过继治疗的免疫细胞群的方法 |
EP3166968B1 (fr) | 2014-05-02 | 2021-09-22 | The Trustees of the University of Pennsylvania | Compositions de récepteurs d'auto-anticorps chimériques et procédés afférents |
TWI805109B (zh) | 2014-08-28 | 2023-06-11 | 美商奇諾治療有限公司 | 對cd19具專一性之抗體及嵌合抗原受體 |
SG10202002324SA (en) | 2014-11-05 | 2020-05-28 | Juno Therapeutics Inc | Methods for transduction and cell processing |
MA45341A (fr) * | 2016-06-06 | 2019-04-10 | Hutchinson Fred Cancer Res | Procédés de traitement de malignités de lymphocytes b au moyen d'une thérapie cellulaire adoptive |
EP3704230B1 (fr) | 2017-11-01 | 2024-10-23 | Juno Therapeutics, Inc. | Procédé de génération de compositions thérapeutiques de cellules modifiées |
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EP3886894A2 (fr) | 2021-10-06 |
SG11202105380RA (en) | 2021-06-29 |
KR20210110811A (ko) | 2021-09-09 |
MX2021006244A (es) | 2021-09-10 |
CA3120363A1 (fr) | 2020-06-04 |
WO2020113188A2 (fr) | 2020-06-04 |
BR112021010120A2 (pt) | 2021-08-31 |
FI3886894T3 (fi) | 2024-05-24 |
DK3886894T3 (da) | 2024-06-03 |
CN113692285A (zh) | 2021-11-23 |
IL316112A (en) | 2024-12-01 |
PL3886894T3 (pl) | 2024-07-01 |
EP4393547A2 (fr) | 2024-07-03 |
ES2986007T3 (es) | 2024-11-08 |
JP2022513689A (ja) | 2022-02-09 |
IL283298B1 (en) | 2024-11-01 |
IL283298A (en) | 2021-07-29 |
US20220031746A1 (en) | 2022-02-03 |
WO2020113188A3 (fr) | 2020-08-06 |
EP4393547A3 (fr) | 2024-09-18 |
PT3886894T (pt) | 2024-05-02 |
EP3886894B1 (fr) | 2024-03-13 |
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